1. Field of the Invention
The present invention relates to the field of microdetector array devices for sensing analytes (molecules and ions). More particularly, methods are provided for placing arrays of molecular and ionic filter material on detector arrays.
2. Background of the Invention
Miniaturization has increased the efficiency of numerous microelectronic processes and detection devices and is contributing to the development and production of smaller, lighter, and faster versions of mechanical, optical, and electronic devices such as computers, cameras, mobile phones, and molecular or ionic detection systems. New technological capabilities in miniaturization have also had a large impact in the area of microsensor arrays. Microsensors have the ability to measure and analyze thousands of differential individual responses that collectively can be used to detect and analyze complex vapor and solution targets. Some examples include “odorprint” detection and blood analyte panels (See for example Barash et al. 2009, Lee et al. U.S. Pat. No. 7,859,029B2, Michel et al. U.S. Pat. No. 5,694,932). A key enabling component of these examples and many other microsensors is the ability to “sensitize” or modify the surface of individual detectors with molecular agents that impart differential functional chemistries to the sensor. “Sensitization” is defined as adding a component to the surface of, or integrally mixing with, the active transducer element of the detector. Sensitization of each detector in the microsensor array then provides differential response patterns for components of complex molecular or ionic mixtures. Methods that involve serial deposition to sensitize individual detectors in an array such as printing, or sequential methods such as lithography, can be slow and costly when the number of detectors in the array is large and the size of individual detectors is small. Both of these attributes are desirable for increasing the detection range (i.e. dynamic range of detection for any or all of the components of the mixture), or detection capacity (sensitivity with which an individual sensor responds to a target, or target component of a mixture.
Likewise, creating microsensor arrays with overall small dimensions provides a means to make more compact sensors which can be used in a number of applications ranging from small waste streams, biomedical in vitro and in vivo devices, discrete environmental monitoring, to name a few. Present methods for making and sensitizing detectors in a microsensor array using “top-down” methods such as photolithography, currently used for the manufacture of the extremely small components in these miniature devices, have slowed progress in this area (Bashir et al., 2001). The use of micro- and nanoscale structure assembly is under evaluation as a means to drive miniaturization of microelectronic and other sensor devices (McNally et al., 2003). These extremely small-scale materials often exhibit properties that are different from their physically larger counterparts. In systems with micro- and nanoscale dimensions, these properties are often “tunable” or adjustable. This can make such systems more useful for specific applications, such as biomedical sensors, industrial fluid stream analysis, targeted drug delivery and molecular detection in air or water. Detector substrates may include arrays of solid-state sensing elements such as chemiresistive arrays composed of carbon nanotube, semiconductors, and conducting polymers (See for example Wang et al. 2008; NIkfarjam et al. 2010; Voronov et al. 2010; Kang et al. 2009; Jiang et al. 2009, Ubaldo et al. U.S. Pat. No. 6,028,331), Field Effect Transistors (FETs) (Wakida et al. 2007, Vijayalakshmi et al. 2008, Kakoschke U.S. Pat. No. 7,786,530, Edinger U.S. Pat. No. 7,335,942), Ion-Selective Field Effect Transistors (ISFETS) (Zehfroosh et al. 2010; Abdullah et al. 2009, Lindner et al. 2009, Kunath U.S. Pat. No. 7,321,143), Thin Film Transistors (TFTs), for example Fortunato et al. 2006, Song-hua et al. 2006, and other ion-specific or electrochemical transducers (Geiling et al. 2006; Mizier 1983, Crumly et al. U.S. Pat. No. 6,849,168, Patel et al. U.S. Pat. No. 7,489,017.
New approaches for making sensing elements that involve solid-state chemiresistive semiconductor structures that are patterned on the nanoscale may also be employed in microsensor arrays. For example, a patent application related to microsensors that is commonly owned with the present application and titled “Imprinted Semiconductor Multiplex Detection Array” was filed on Jan. 11, 2011 (App. No. 13004381).
Positional assembly of arrays of exceedingly small micro- and nanoscale unit components by conventional manufacturing techniques is exceedingly difficult. As such, cost-effective and mass manufacture of such devices has not yet been realized. Therefore, the discovery and development of novel methods for “bottom-up” fabrication has recently emerged as an active field of study. A need exists to adopt efficient fabrication and manufacturing procedures for the production of new and useful, micro- and nanoscale devices.
Specifically, what is needed is a process for expanding, the parallel detection capabilities of microsensor arrays to enhance the selectivity, sensitivity, dynamic range, and background rejection capabilities in measurement of the signatures of complex gas, liquid or molecular and ionic solution mixtures directly on the detector array, or onto a substrate that can be applied, or transferred to the detector array. Methods that enable the manufacturing of dense and overall compact microsensor arrays will enhance numerous applications in molecular and ionic detection of complex mixtures and solutions. More particularly, methods that will lead to the deposition of the sensitization moiety on each sensor in the array during a single batch processing step are desired.
The efficient manufacture of micro- and nanoscale structures for use as miniature filter devices is made possible by the use of assembled arrays, which provide a means for the assembly of micro- and nanoscale filters with precisely positioned functional subunits. Efficient detection of components of various mixtures is enhanced by the filtration of mixtures prior to detection with micro- and nanoscale detection devices. The manufacture, using biomolecule-guided assembly, of functional micro- and nanoscale filters and their use for various applications such as complex gas and ionic solution mixture analysis is disclosed. Commercial detection systems are limited to the packaging of arrays of relatively large individual sensors which include macroscopic filter particles packaged over the sensor, see for example Figaro, Arlington Heights, Ill., USA, and Portsmouth Hampshire, United Kingdom, and Axion Biosystems, Atlanta, Ga., USA.
As used herein, a “filter array” or a “filter particle array” refers to an array of particles on a surface that removes or reduces an amount of a component from a mixture that traverses the array. As used herein, “traverse” means passing through, over, or across. “Filtering” is used herein to mean reducing the amount or concentration of at least one component of a mixture or removing or depleting at least one component of a mixture. “Filtering” may occur by the movement of a mixture through, across, or over a filter of the invention. “Removing” or “removal” is meant to refer to complete or partial depletion of a component in a mixture, or retardation of the traversal rate of one or more components of the mixture giving rise to a delay in the temporal detection of one component relative to another. The terms “reducing”, “removing”, “depleting”, “retarding” or “filtering” or any variation of these terms are used interchangeably, and when used in the claims and/or the specification mean causing any decrease in the amount or concentration of at least one component of a mixture to achieve a desired result. As used herein, the term “filtrate” refers to the components of a filtered mixture that have traversed a filter array.
In aspects of the invention, filter particles may cause filtering, by binding, absorbing, reflecting, repelling, excluding, or encapsulating a component or by engaging in a reaction, such as a chemical reaction, which modifies or destroys a component of a mixture or transforms it into sub-components or other components. These actions may prevent or reduce the passage of a component through a filter or reduce or eliminate the component from the mixture following filtration.
For the purposes of the invention, a “mixture” refers to a composition having two or more different components. In an aspect of the invention, one or more components of a mixture retain their own properties and makeup. In another aspect, two or more components of a mixture may interact and produce a mixture with properties distinct from those of the individual components. In yet another aspect of the invention, a mixture may comprise a combination of components including those that retain their properties when combined with other components and those that interact with other components upon combining and have properties distinct from those of the components prior to combining. In aspects of the invention, all components of a mixture may not be known prior to or after filtration. Mixture may refer to a combination of components prior to or after filtration. Similarly, a filtrate may comprise a mixture of components.
A filter particle array may filter many types of mixtures. Mixtures may occur as blends, solutions including ionic solutions, suspensions, or colloids and may comprise one or more of a liquid, a solid, a gas, a biomolecule or combinations thereof. Mixtures may comprise, for example, molecular gaseous species, inorganic compounds, organic compounds, biomolecules, ionic molecules, or combinations of these. Simple mixtures (containing only a few components) or complex mixtures (containing numerous components) may be filtered using filter arrays of the invention.
The components of a mixture that are filtered using methods of the invention may be separated or partially separated after filtration. In some aspects of the invention, fewer components are present in the filtrate than were present in the mixture prior to filtration. In other aspects, the filtrate may contain a lower concentration or amount of one or more component than was present in the mixture prior to filtration.